Ghrelin, pancreatic polypeptide plasma concentrations and gastric myoelectric activity in celiac disease.

BACKGROUND/AIMS: The aim of the study was to analyze the effect of celiac disease(CED) on the upper-gut motility and release of enteral hormones (ghrelin and pancreatic peptide (PP)). MATERIALS AND METHODS: the study included 25 patients diagnosed with CED and 30 healthy controls. Gastric myoelectric activities (EGG) in a fasted and fed state were recorded. The plasma concentrations of ghrelin and PP were determined. R e s u l t s: CED patients presented in a fasted state a decreased percentage of normogastria 54.8 ± 24.5 vs. 86 ± 12.3%, p = 0.02 and slow wave coupling (SWC) 52.7 ± 13.4 vs. 77.4 ± 11.9%; p = 0.00001 with increased dominant power (DP) 11.6 ± 1.5 vs. 11.1 ± 1.1. Contrary to the controls, they did not show an improvement in the percentage of normogastria, DP and SWC when examined in a fed state (p 〈0.05). Furthermore, CED patients presented with significantly lower fasting plasma concentrations of ghrelin 156.8 ± 86.7 vs. 260.2 ± 87.6 pg/ml, p = 0.0002 and significantly higher fasting PP levels than did the controls 265.2 ± 306.3 vs. 54.1 ± 54.6 pg/ml, p = 0.0005. C o n c l u s i o n: CED affects gastric myoelectric activity (decreasing normogastria and coupling) and causes changes in fasting concentrations of enteral hormones (decrease in ghrelin and an increase in PP). Gastric myoelectric response to food is abolished in CED patients, probably due to the neurohormonal changes induced by primary inflammation associated with this disease.

[Antibodies against alfa-enolase as an indication of inflammatory process in patients with celiac disease--preliminary results]. / Przeciwciala przeciw alfa enolazie, jako wskaznik stanu zapalnego u chorych na celiakie-doniesienie wstepne.

INTRODUCTION: Celiac disease (CD) is an autoimmunological gluten sensitive enteropathy occuring to genetically predisposed individuals. Active CD is accompanied by presence of multiple antibodies. Anti alpha enolase antibodies were reported in several autoimmunological disorders like rheumatoid arthritis, primary sclerosing cholangitis. Data about its presence and role in CD is avaricious. AIM: The aim of this study was to determine presence of anti alpha enolase antibodies in CD, correlation with gluten exposure, presence of anti tranglutaminase antibodies and Marsh scale. METHODS: Sera from 31 patients with CD (21 females, 10 males) and 6 healthy subjects were collected. Evaluation of CD activity and adherence to gluten free diet were obtained by serology tests (presence of endomyslum antibodies and/or anti transglutamineses in IgA or IgG classes) and histological hallmarks. Anti alpha enolase antibodies were identified in sera using ELISA kit. Titres of anti alpha enolase antibodies were identified among patients with newly diagnosed CD, CD patients non adhering to gluten free diet (GFD), adhering to GFD and among healthy subjects. RESULTS: Mean titre of anti alpha enolase antibodies was higher in CD patients (both treated and non treated) in comparison to control group, respectively 1.1 ng/mL, and 0.795 ngl mL. Among CD patients non adhering to gluten free diet mean titre was 1.4 ng/mL. CONCLUSIONS: Higher anti alpha enolase antibodies titres in non treated CD suggest usefulness of its measurement. These antibodies might be a novel marker of chronic inflammation among CD patients non adhering to GFD.

[Endoscopic and histopathological findings of the upper gastrointestinal tract in patients with functional and organic dyspepsia]. / Zmiany endoskopowe i histopatologiczne górnego odcinka przewodu pokarmowego u chorych z dyspepsja organiczna i czynnosciowa.

INTRODUCTION: Endoscopic examination of the upper gastrointestinal tract (upper GI) with macroscopic and histopathological evaluation provides essential tool to differentiate the organic and functional causes of dyspepsia. The distinction, however, is often smooth and not fully defined. The aim of this study was to assess the frequency and type of the macroscopic and histopathological changes in the upper GI endoscopy in patients with symptoms of dyspepsia. MATERIAL AND METHODS: A retrospective study was performed on 212 patients with dyspepsia, at the age of 18-84 years, including 60 patients to 45 years of age (group I) and 152 patients older than 45 (group II) who underwent gastroscopy. The severity of esophagitis was classified according to the Los Angeles Classification and gastritis according the updated Sydney system. Biopsy specimens were taken from the gastric and duodenum for histopathological examination. The presence of H. pylori infection has been established on the basis of histopathological examination and positive rapid urease test. RESULTS: Reflux esophagitis was found in 18 patients (8.5%), slightly more common in people over 45 years of age (group I--5%, group II--9.2%). The mild forms of esophagitis occurred most frequently. A more advanced form of inflammation and Barrett's esophagus was found only in patients over 45 years of age. Normal gastric and duodenal mucosa was revealed in 30% of patients in group I and 9.2% in group II. The most common endoscopic lesion was gastritis, mostly erythematous-exudative and less often atrophic. The presence of H. pylori infection was varied in the different types of inflammation. H. pylori infection occurred most frequently in the case of erosive and follicular gastropathy. The most common location of H. pylori infec- frequent in older patients. Peptic ulcer was found in 4.7% of patients (group I--5%, group II--4.6%). In one patient (61 years old) stomach cancer was diagnosed and in one patient (<45 years old) Crohn's disease of the upper GI was diagnosed. The majority of patients had normal duodenal mucosa. In 3.3% of patients (group I--8.3%, group II--1.3%), who had not previously diagnosed celiac disease, histopathological changes typical of celiac disease has been shown. In all patients, in whom biopsy specimens were taken from normal duodenal mucosa (14% of patients), histopathological examination revealed the presence of non-specific inflammation, regardless of the coexistence of H. pylori infection. CONCLUSION: Regardless of the severity of lesions of the upper GI endoscopy in patients with dyspepsia, it is advisable to take biopsy from the gastric and duodenal mucosa, which allows for an individualized management of these patients. Celiac disease should be considered in the diagnosis of the causes of dyspepsia. Further studies of microscopic duodenitis in patients with dyspepsia are needed.

Postprandial effect of gastrointestinal hormones and gastric activity in patients with irritable bowel syndrome.

Altered gut regulation, including motor and secretory mechanisms, is characteristic of irritable bowel syndrome (IBS). The severity of postprandial symptoms in IBS patients is associated with discomfort and pain; gas-related symptoms such as bloating and abdominal distension; and abnormal colonic motility. The aim of this study was to assess the postprandial response, i.e., gut peptide secretion and gastric myoelectric activity, in patients with constipation-predominant IBS. The study was conducted on 42 IBS patients (14 males, 28 females, mean age 45.1 ± 15.3 years) and 42 healthy participants (16 males, 26 females, mean age 41.1 ± 8.7 years). The study assessed plasma gut peptide levels (gastrin, CCK-Cholecystokinin, VIP-Vasoactive Intestinal Peptide, ghrelin, insulin) and gastric myoelectric activity obtained from electrogastrography (EGG) in the preprandial and postprandial period (meal-oral nutritional supplement 300 kcal/300 ml). Mean preprandial gastrin and insulin levels were significantly elevated in IBS patients compared to the control group (gastrin: 72.27 ± 26.89 vs. 12.27 ± 4.91 pg/ml; p < 0.00001 and insulin: 15.31 ± 12.92 vs. 8.04 ± 3.21 IU/ml; p = 0.0001), while VIP and ghrelin levels were decreased in IBS patients (VIP: 6.69 ± 4.68 vs. 27.26 ± 21.51 ng/ml; p = 0.0001 and ghrelin: 176.01 ± 88.47 vs. 250.24 ± 84.55 pg/ml; p < 0.0001). A nonsignificant change in the CCK level was observed. IBS patients showed significant changes in postprandial hormone levels compared to the preprandial state-specifically, there were increases in gastrin (p = 0.000), CCK (p < 0.0001), VIP (p < 0.0001), ghrelin (p = 0.000) and insulin (p < 0.0001). Patients with IBS showed reduced preprandial and postprandial normogastria (59.8 ± 22.0 vs. 66.3 ± 20.2%) compared to control values (83.19 ± 16.7%; p < 0.0001 vs. 86.1 ± 9.4%; p < 0.0001). In response to the meal, we did not observe an increase in the percentage of normogastria or the average percentage slow-wave coupling (APSWC) in IBS patients. The postprandial to preprandial power ratio (PR) indicates alterations in gastric contractions; in controls, PR = 2.7, whereas in IBS patients, PR = 1.7, which was significantly lower (p = 0.00009). This ratio reflects a decrease in gastric contractility. Disturbances in the postprandial concentration of gut peptides (gastrin, insulin and ghrelin) in plasma may contribute to abnormal gastric function and consequently intestinal motility, which are manifested in the intensification of clinical symptoms, such as visceral hypersensitivity or irregular bowel movements in IBS patients.

Serum levels of selected micronutrients in patients with inflammatory bowel disease in clinical remission.

INTRODUCTION: Patients with inflammatory bowel disease (IBD) can experience micronutrient deficiency regardless of disease activity and extent. OBJECTIVES: We aimed to evaluate serum concentrations of selected trace elements in adult patients with IBD in clinical remission with involvement limited to the colon who received immunosuppressive treatment. PATIENTS AND METHODS: We enrolled 32 patients with IBD (mean [SD] age, 41 [15.2] years) and 30 healthy controls (mean [SD] age, 39.1 [11.8] years). Serum selenium, iron, copper, and zinc levels as well as complete blood count were measured in both groups. RESULTS: Patients with IBD had lower zinc concentrations than controls (mean [SD], 0.76 [0.13] mg/l vs 0.83 [0.13] mg/l; P = 0.047). No differences were observed for selenium (mean [SD], 0.90 [0.24] µmol/l vs 0.93 [0.19] µmol/l) and copper levels (mean [SD], 1.03 [0.27] mg/l vs 0.97 [0.22] mg/l). Compared with controls, patients with IBD had lower red blood cell count (mean [SD], 4.4 [0.6] 106/µl vs 4.7 [0.4] 106/µl; P = 0.03), hemoglobin (mean [SD], 12.7 [2.2] g/dl vs 14.3 [0.8] g/dl; P = 0.001), and iron levels (mean [SD], 14.2 [9.4] µmol/l vs 23.4 [2.7] µmol/l; P = 0.0001). Patients with IBD showed a positive correlation between selenium and iron (R = 0.499; P = 0.004) as well as selenium and hemoglobin levels (R = 0.579; P = 0.001). CONCLUSIONS: Patients with IBD, despite maintaining clinical remission, should undergo systematic laboratory test for anemia or micronutrient deficiencies.

Effect of long-term proton pump inhibitor therapy on complete blood count parameters and selected trace elements: a pilot study.

INTRODUCTION: Proton pump inhibitors (PPIs) are widely prescribed for several gastrointestinal conditions, often as long­term therapy. The effects of term PPI use have not been fully elucidated. OBJECTIVES: We aimed to determine the association between long­term PPI use and complete blood count parameters, particularly red blood cell (RBC) count, white blood cell (WBC) count, and hemoglobin concentrations, as well as serum levels of selected micronutrients such as selenium (Se), iron (Fe), copper (Cu), and zinc (Zn). PATIENTS AND METHODS: We enrolled 37 patients on long­ term PPI therapy (mean [SD] age, 57.1 [15.4] years) and 30 healthy controls (mean [SD] age, 39.3 [11.8] years). In each group, complete blood count, and serum Fe levels were performed, and serum Cu, Zn, and Se levels were measured using atomic absorption spectrometry. RESULTS: Red blood cell and WBC counts were lower in the PPI group compared with controls (mean [SD], 4.24 [0.55] ×106/µl vs 4.7 [0.4] ×106/µl; P <0.001 and 6.13 [1.44] ×103/µl vs 7.3 [1.28] ×103/µl; P <0.001, respectively). Hemoglobin and serum Fe concentrations were also lower in the PPI group (mean [SD], 12.5 [1.8] g /dl vs 14.3 [0.8] g /dl; P <0.001 and 16.3 [5.4] µmol/l vs 23.4 [2.7] µmol/l; P <0.001, respectively). Serum Zn and Cu concentrations were higher in PPI users than in controls. CONCLUSIONS: Long­term PPI therapy may reduce RBC and WBC counts as well as hemoglobin levels, leading to iron deficiency. It may also aff ect concentrations of some micronutrients, although the underlying mechanism of this association is not fully clear.

Associations between chronotype, sleep disturbances and seasonality with fatigue and inflammatory bowel disease symptoms.

Growing number of studies suggests link between circadian rhythms and inflammatory bowel diseases (IBD) manifestation. We hypothesize that: 1) IBD are associated with increased eveningness and sleep disturbances; 2) eveningness and sleep disturbances are related to more severe IBD symptoms. In total, 129 participants were enrolled to this study, divided into three groups: 34 Crohn's disease (CD) patients, 38 ulcerative colitis (UC) patients and 57 healthy controls (HC) group. They all fulfilled a questionnaire, consisting of the Composite Scale of Morningness (CSM), Seasonal Pattern Assessment Questionnaire (SPAQ), Pittsburgh Sleep Quality Index, Inflammatory Bowel Disease Questionnaire (IBDQ) and Multidimensional Fatigue Inventory (MFI). Multiple regression models controlled for age and sex revealed that in CD group higher eveningness measured with CSM was associated with higher general fatigue, physical fatigue, mental fatigue and reduced motivation measured by MFI. Lower CSM morning affect is associated with greater general fatigue, physical fatigue and more reduced activity. Greater seasonality scores are associated with increased physical fatigue and more reduced activity and motivation. Lower sleep quality measured with PSQI is associated with higher physical fatigue and more reduced activity. Correlational analysis revealed that higher seasonality and lower sleep quality are associated with increased systemic and bowel symptoms and decreased emotional and social functions measured with IBDQ. In UC group, eveningness is associated with greater general fatigue, physical fatigue and more reduced activity. Higher CSM morning affect is associated with decreased general fatigue, physical fatigue and less reduced activity. Higher CSM circadian preference scores are associated with decreased general and physical fatigue, and less reduced activity. Increased seasonality is associated with more physical fatigue. Lower sleep quality is associated with greater general and physical fatigue. To our best knowledge this is the first study evaluating associations between chronotype and sleep disturbances with IBD symptoms. We have found that chronotype preferences, whose role in IBD has been until now overlooked, may be one of the important factors contributing to fatigue in this clinical group.

Intestinal parameters of oxidative imbalance in celiac adults with extraintestinal manifestations.

AIM: To evaluate selected intestinal parameters of oxidative stress, and antioxidant capacity in adult celiac disease patients with extraintestinal manifestations. METHODS: The study involved 85 adult patients divided into the following subgroups: (1) patients with newly diagnosed celiac disease (CD) (n = 7); (2) celiac patients not adhering to a gluten-free diet (GFD) (n = 22); (3) patients with CD on the GFD (n = 31); and (4) patients with functional disorders of the gastrointestinal tract, serving as controls (n = 25). Celiac patients presented with non-classic symptoms or extraintestinal manifestations. Standard blood tests including serum antioxidant levels (uric acid, bilirubin, and vitamin D), celiac antibody levels, and histopathological status of duodenal biopsy specimens have been determined. The expression of mRNA for tumor necrosis factor α (TNF-α), interleukin 1ß (IL-1ß), interleukin 10 (IL-10), superoxide dismutase (SOD), heat-shock protein 70 (HSP-70), hypoxia-inducible factor 1 (HIF-1α), and BAX in the duodenal mucosa of patients was analyzed by reverse transcriptase-polymerase chain reaction. RESULTS: The mean plasma uric acid level in patients with active CD (newly diagnosed and nonadherent patients) and treated celiac patients was significantly higher than in controls (260.17 ± 53.65 vs 190.8 ± 22.98, P < 0.001, and 261.7 ± 51.79 vs 190.8 ± 22.98, P < 0.001, respectively). The mean bilirubin concentration in active and treated celiac patients was significantly lower than in controls (8.23 ± 5.04 vs 10.48 ± 4.08, P < 0.05 and 8.06 ± 3.31 vs 10.48 ± 4.08, P < 0.05, respectively). The mean plasma vitamin D level was significantly lower in active celiac patients than in treated celiac patients and controls (19.37 ± 9.03 vs 25.15 ± 11.2, P < 0.05 and 19.37 ± 9.03 vs 29.67 ± 5.12, P < 0.001, respectively). The expression of TNF-α, IL-10, and HSP-70 mRNAs was significantly elevated in the celiac groups regardless of the diet when compared with controls. Patients on the GFD presented a significantly lower mRNA expression of TNF-α and IL-10 than in newly diagnosed and nonadherent patients (P < 0.05). The expression of SOD mRNA was significantly elevated in celiac patients compared with controls (P < 0.05), with a significant difference between treated and untreated patients (P < 0.05). The expression of HIF-1α mRNA and BAX mRNA was significantly higher in patients with active CD compared with controls and patients on GFD, while no difference was observed between the latter two groups. CONCLUSION: Increased intestinal expression of HSP-70 despite GFD indicates that GFD only partially reduced oxidative stress. CD patients exhibited an oxidative imbalance and inflammatory response despite GFD. Uric acid may act as an important antioxidant in CD.

Alterations in serum levels of selected markers of oxidative imbalance in adult celiac patients with extraintestinal manifestations: a pilot study.

INTRODUCTION    Oxidative stress is considered to be one of the mechanisms responsible for gluten toxicity, but its role in celiac disease (CD) remains unclear. OBJECTIVES    The aim of the study was to evaluate oxidative imbalance in the pathomechanism of CD by determining the concentrations of nitric oxide (NO) and selected antioxidant parameters. PATIENTS AND METHODS    The study involved 197 adult patients: 53 patients with untreated active CD, 92 celiac patients on gluten­free diet (GFD), and 52 controls. The serum levels of antioxidants (uric acid, bilirubin, ferritin, albumin), celiac antibodies, NO, glutathione peroxidase 3 (GPx3), and vitamin E were measured. A histopathological study of duodenal biopsy was performed. RESULTS    Celiac patients had higher uric acid concentrations than controls (P <0.001). NO levels were higher in patients with active CD than in controls (P <0.01) and were correlated with the degree of mucosal damage (r2 = 0.04; P = 0.01). Vitamin E levels were decreased in celiac patients (P <0.01), and GPx3 activity was reduced in patients with active CD compared with controls (P <0.001). CONCLUSIONS    Oxidative imbalance may be involved in the pathomechanism of CD in adults. GFD only partially reduces oxidative stress. Serum NO levels seem to be a marker of the effectiveness of treatment. Uric acid may act as an antioxidant in CD.

Concentrations of antiganglioside M1 antibodies, neuron-specific enolase, and interleukin 10 as potential markers of autonomic nervous system impairment in celiac disease.

INTRODUCTION Celiac disease (CD) is an immune-mediated enteropathy related to permanent gluten intolerance, characterized by gastrointestinal symptoms as well as nongastrointestinal symptoms, including neurologic ones. The presence of neuron-specific enolase (NSE), interleukin 10 (IL-10), and antiganglioside M1 (anti-GM1) antibodies has been demonstrated for neurologic conditions as well as immune disorders with neurologic manifestations. OBJECTIVES The aim of the study was to determine the concentrations of IL-10, NSE, and anti-GM1 antibodies in the course of CD and their correlation with changes in electrogastrography (EGG) and with heart rate variability (HRV). PATIENTS AND METHODS The study included 68 participants: 34 patients with CD and 34 healthy individuals. We assessed the concentrations of IL-10 and NSE as well as the presence of anti-GM1 antibodies in serum. We investigated correlations between the concentrations of IL-10, NSE, and anti-GM1 antibodies and the results of EGG and HRV. RESULTS Patients with CD had a higher level of anti-GM1 antibodies than controls (1.38 ng/ml [0.98-2.03 ng/ml] vs 0.81 ng/ml [0.35-1.15 ng/ml]). Median IL-10 concentrations in patients with CD differed significantly from those in controls (7 pg/ml [4.33-11.48 pg/ml] vs 4.27 pg/ml [2.44-7 pg/ml]; P = 0.010). In HRV analysis, a positive correlation between IL-10 concentrations and very low frequency spectrum was observed (r = 0.63; P = 0.003). There was no correlation between the concentrations of IL-10, NSE, or anti-GM1 antibodies and EGG parameters. CONCLUSIONS Chronic inflammation in the course of CD may lead to autonomic nervous system impairment and development of neurologic disorders. Therefore, anti-GM1 antibodies and IL-10 may be considered as markers of nervous system impairment in the course of CD.